RT Journal Article
SR Electronic
T1 Binding specificities of human RNA binding proteins towards structured and linear RNA sequences
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 317909
DO 10.1101/317909
A1 Arttu Jolma
A1 Jilin Zhang
A1 Estefania Mondragón
A1 Ekaterina Morgunova
A1 Teemu Kivioja
A1 Kaitlin U. Laverty
A1 Yimeng Yin
A1 Fangjie Zhu
A1 Gleb Bourenkov
A1 Quaid Morris
A1 Timothy R. Hughes
A1 Louis James Maher III
A1 Jussi Taipale
YR 2020
UL http://biorxiv.org/content/early/2020/04/25/317909.abstract
AB Sequence specific RNA-binding proteins (RBPs) control many important processes affecting gene expression. They regulate RNA metabolism at multiple levels, by affecting splicing of nascent transcripts, RNA folding, base modification, transport, localization, translation and stability. Despite their central role in most aspects of RNA metabolism and function, most RBP binding specificities remain unknown or incompletely defined. To address this, we have assembled a genome-scale collection of RBPs and their RNA binding domains (RBDs), and assessed their specificities using high throughput RNA-SELEX (HTR-SELEX). Approximately 70% of RBPs for which we obtained a motif bound to short linear sequences, whereas ~30% preferred structured motifs folding into stem-loops. We also found that many RBPs can bind to multiple distinctly different motifs. Analysis of the matches of the motifs in human genomic sequences suggested novel roles for many RBPs. We found that three cytoplasmic proteins, ZC3H12A, ZC3H12B and ZC3H12C bound to motifs resembling the splice donor sequence, suggesting that these proteins are involved in degradation of cytoplasmic viral and/or unspliced transcripts. Surprisingly, structural analysis revealed that the RNA motif was not bound by the conventional C3H1 RNA-binding domain of ZC3H12B. Instead, the RNA motif was bound by the ZC3H12B’s PilT N-terminus (PIN) RNase domain, revealing a potential mechanism by which unconventional RNA binding domains containing active sites or molecule-binding pockets could interact with short, structured RNA molecules. Our collection containing 145 high resolution binding specificity models for 86 RBPs is the largest systematic resource for the analysis of human RBPs, and will greatly facilitate future analysis of the various biological roles of this important class of proteins.Competing Interest StatementThe authors have declared no competing interest.